This project continues our studies of the cellular interactions involved in skin allograft rejection. The focus of our studies is the ability of phenotypically distinct, class I specific Th cells to participate in the rejection of class I disparate skin grafts. We have previously established the importance of Lyt2+ TH in the rejection of class I disparate grafts. Further, we have shown that L3T4+ class I specific Th fail to participate in the rejection of these grafts because of the failure of a single epidermal cell population to express the determinants necessary for their activation. We are currently exploring the conditions under which these class I specific L3T4+ Th can be activated in vivo. We have taken two approaches: the first involves attempts to increase the expression of the determinants known to trigger this cell on epidermal cells, and second, to trigger these cells by a route other than skin grafting. A second phase of the project explored the abilities of phenotypically distinct Th populations to interact with separate effector cell populations in rejecting skin grafts. This was assessed by measuring whether these TH populations could collaborate with effector cells of a different specificity. We have previously demonstrated the ability of L3T4+ Th specific for class II determinants to function in this way. However, Lyt2+ class I specific helpers fail to do so, suggesting that they may induce graft rejection via a "dual function" mechanism.